Osteoarthritis, Knee
Conditions
Keywords
osteoarthritis, knee
Brief summary
The study is being conducted to investigate the safety and activity of TissueGene-C injected into the knee joint of patients with chronic degenerative joint disease (DJD) who will be undergoing total knee replacement.
Detailed description
The purpose of this first human study is to investigate the safety and biological activity of intra-articularly applied TissueGene-C in patients with chronic degenerative joint disease (DJD) who will be undergoing total knee replacement. In addition, data on joint pain, range of motion, and functionality will be obtained in this patient population prior to total knee replacement. The primary objective of this study is to evaluate the safety and biological activity of intra-articularly administered TissueGene-C as evidenced by observation of the injection site for irritation or other abnormalities affecting the incidence and severity of adverse events, and the changes in physical examination findings and laboratory tests as compared to the placebo control. The secondary objectives of this study are to: 1. Evaluate the dose response of the hChonJb#7 cells in grafting at the defect as compared to the placebo control. 2. Evaluate distribution of hChonJb#7 cells out of the injection site. 3. Evaluate the regeneration of hyaline cartilage as determined by the histological analysis of the resected knee tissue. 4. Evaluate the joint for evidence of tissue overgrowth or transformation. 5. Evaluate the biological activity of TissueGene-C on joint pain, range of motion and functionality as compared to the placebo control
Interventions
BIOLOGICALTissueGene-C
TissueGene-C at 3x10e6, 1x10e7 or 3x10e7 cells/joint to be administered by intra-articular injection
BIOLOGICALPlacebo
Placebo control (DMEM)
Sponsors
Kolon TissueGene, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female subjects 2. Age 18 years and older 3. In general good health as evidenced by physical examination, normal hematology, serum chemistry, and urinalysis screening laboratory results, and a negative history of significant organ system disorders. All laboratory values must be within 20% of normal ranges. 4. Patients with Degenerative Joint Disease (DJD) of the knee that is refractory to existing drug therapies and who are scheduled for Total Knee Arthroplasty. 5. Based on Radiographic findings, defect should be more than 2 cm. 6. Patients providing written informed consent, after the nature of the study, are fully explained. 7. Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women. 8. Blood Pressure measurements - Systolic Blood Pressure (SBP) should be between 90-160mm. Hg, and Diastolic Blood Pressure (DBP) between 50-90mm.Hg, 9. Osteoarthritis confirmed by the Radiographic Criteria of Kellgren and Lawrence 10. Symptom of pain for more than four (4) consecutive months and intensity greater than Grade 4 on the 11-point numeric scale.
Exclusion criteria
1. Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results 2. Patients taking anti-inflammatory medications (prescription or over-the-counter), including herbal therapies, within 14 days of baseline visit 3. Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug/alcohol test at the time of screening 4. Patients receiving injections to the treated knee within 2 months prior to study entry 5. Patients who are pregnant or currently breast-feeding children 6. Patients with systemic, rheumatic, or inflammatory disease of the knee or chondrocalcinosis, hemochromatosis, inflammatory arthritis, necrosis of the femoral condyle, arthropathy of the knee associated with juxta-articular Paget's disease of the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's knee joint, villonodular synovitis, and synovial chondromatosis. 7. Patients with ongoing infectious disease, including HIV and hepatitis 8. Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes 9. Patients participating in a study of an experimental drug or medical device within 30 days of study entry. 10. Positive drug screen at screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Adverse Events | Through 28 days post-dosing | The incidence of observations at the site of administration and the incidence adverse events assessed through 28 days after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Showing Engraftment at the Defect | 28 Days | Dose Response of the TG-C in Engrafting at the Defect as Compared to Placebo Control |
| Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | 12 Months | Number of Patients with Distribution of hChonJb#7 Cells Detected Outside of the Injection Site as determined by PCR analysis for vector DNA. |
| Number of Participants With Observable Evidence of Cartilage Regeneration | Days 0, 3, 7, 11, 28 (prior to surgery), and day 29 (one day post-surgery) following dosing. Follow-up patient monitoring will be performed at 3, 6, 9, and 12 months following dosing | The evaluation of regeneration of hyaline cartilage as determined by histological analysis of resected knee tissue and observation for engraftment and cartilage production. |
| Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | 29 | Visual and histological analysis of knee joint tissues to determine the number of patients with tissue overgrowth or transformation |
| Number of Patients With Improvements in Pain and Function of the Knee Joint | 28 Days | Assessment of the number of patients with improvement in pain and function of the knee joint |
Countries
United States
Participant flow
Pre-assignment details
Enrollment and assignment of patients in Arms 2 and 3 (dose escalation to sequentially higher doses) was only performed after completion of review of safety data in the previous Arm (lower dose) by the Independent Data Monitoring Committee
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment (TG-C) TissueGene-C at 3x10e6, 1x10e7 or, 3x10e7 cells/joint
TissueGene-C: TissueGene-C at 3x10e6, 1x10e7 or 3x10e7 cells/joint to be administered by intra-articular injection | 9 |
| Placebo Control (DMEM) Placebo control
Placebo: Placebo control (DMEM) | 3 |
| Total | 12 |
Baseline characteristics
| Characteristic | Placebo Control (DMEM) | Active Treatment (TG-C) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 7 Participants | 10 Participants |
| Age, Continuous | 60.0 Years | 61.0 Years | 60.5 Years |
| Region of Enrollment United States | 3 participants | 9 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 9 | 2 / 3 |
| serious Total, serious adverse events | 0 / 9 | 0 / 3 |
Outcome results
Primary
Summary of Adverse Events
The incidence of observations at the site of administration and the incidence adverse events assessed through 28 days after treatment.
Time frame: Through 28 days post-dosing
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Summary of Adverse Events | 2 Adverse events |
| Active Treatment (TG-C) 2 | Summary of Adverse Events | 2 Adverse events |
| Active Treatment (TG-C) 3 | Summary of Adverse Events | 3 Adverse events |
| Placebo Control (DMEM) | Summary of Adverse Events | 2 Adverse events |
Secondary
Number of Participants With Observable Evidence of Cartilage Regeneration
The evaluation of regeneration of hyaline cartilage as determined by histological analysis of resected knee tissue and observation for engraftment and cartilage production.
Time frame: Days 0, 3, 7, 11, 28 (prior to surgery), and day 29 (one day post-surgery) following dosing. Follow-up patient monitoring will be performed at 3, 6, 9, and 12 months following dosing
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Number of Participants With Observable Evidence of Cartilage Regeneration | 0 participants |
| Active Treatment (TG-C) 2 | Number of Participants With Observable Evidence of Cartilage Regeneration | 0 participants |
| Active Treatment (TG-C) 3 | Number of Participants With Observable Evidence of Cartilage Regeneration | 0 participants |
| Placebo Control (DMEM) | Number of Participants With Observable Evidence of Cartilage Regeneration | 0 participants |
Secondary
Number of Patients Showing Engraftment at the Defect
Dose Response of the TG-C in Engrafting at the Defect as Compared to Placebo Control
Time frame: 28 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Number of Patients Showing Engraftment at the Defect | 0 participants |
| Active Treatment (TG-C) 2 | Number of Patients Showing Engraftment at the Defect | 0 participants |
| Active Treatment (TG-C) 3 | Number of Patients Showing Engraftment at the Defect | 0 participants |
| Placebo Control (DMEM) | Number of Patients Showing Engraftment at the Defect | 0 participants |
Secondary
Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site
Number of Patients with Distribution of hChonJb#7 Cells Detected Outside of the Injection Site as determined by PCR analysis for vector DNA.
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | 0 participants |
| Active Treatment (TG-C) 2 | Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | 0 participants |
| Active Treatment (TG-C) 3 | Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | 0 participants |
| Placebo Control (DMEM) | Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | 0 participants |
Secondary
Number of Patients With Improvements in Pain and Function of the Knee Joint
Assessment of the number of patients with improvement in pain and function of the knee joint
Time frame: 28 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Number of Patients With Improvements in Pain and Function of the Knee Joint | 3 participants |
| Active Treatment (TG-C) 2 | Number of Patients With Improvements in Pain and Function of the Knee Joint | 3 participants |
| Active Treatment (TG-C) 3 | Number of Patients With Improvements in Pain and Function of the Knee Joint | 3 participants |
| Placebo Control (DMEM) | Number of Patients With Improvements in Pain and Function of the Knee Joint | 3 participants |
Secondary
Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint
Visual and histological analysis of knee joint tissues to determine the number of patients with tissue overgrowth or transformation
Time frame: 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Treatment (TG-C) 1 | Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | 0 participants |
| Active Treatment (TG-C) 2 | Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | 0 participants |
| Active Treatment (TG-C) 3 | Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | 0 participants |
| Placebo Control (DMEM) | Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | 0 participants |